nach oben

Irish Journal of Medical Science (1971 -)

Erschienen in:

01.04.2020 | Original Article

Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury

verfasst von: Nilgun Eroglu, Erol Erduran, Gokce Pinar Reis, Aysenur Bahadır

Erschienen in: Irish Journal of Medical Science (1971 -) | Ausgabe 4/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

N-acetylcysteine (NAC) may be useful in the management of chemotherapy-induced liver injury.

Aims

The present study evaluates the possible therapeutic effects of NAC on chemotherapy-induced hepatotoxicity.

Methods

A total of 102 patients’ files who were diagnosed with cancer between 2015 and 2019 were evaluated retrospectively. Two patient groups with and without NAC were selected. NAC was administered in a 3-μg/kg IV dose in a 24-h infusion to 70 patients when any alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) values reached three times the normal levels. The other group consisted of 32 patients who were not treated with NAC. Alanine aminotransferase and GGT values were recorded at pretreatment, and on the 1st, 3rd, 5th, and 7th days in both the NAC and non-NAC groups from files.

Results

In the NAC group, ALT and GGT values on day 1, 3, 5, and 7 differed from each other, decreasing from day 1 to day 7. A statistically significant difference was noted between the values in the NAC group (p < 0.001). In the non-NAC group, the ALT values on day 7 were lower than the ALT values on day 1. A comparison of the ALT and GGT values in the NAC and non-NAC groups found that the values in the NAC group decreased earlier than in the non-NAC group.

Conclusions

This study shows that NAC has a therapeutic effect on hepatotoxicity in children being treated with chemotherapeutic agents due to underlying malign diseases. The early reduction in the results of liver function tests is important for the continuation of chemotherapy.

Ranjeeta B, Rajender Reddy K (2014) Drug-induced liver injury due to cancer chemotherapeutic agents. Semin Liver Dis 34:162–171. https://doi.org/10.1055/s-0034-1375957CrossRef

Sabuncuoğlu S, Ozgunes H (2011) Chemotherapy, free radicals and oxidative stress. Hacet Univ Fac Pharm J 31:137–150

Weijl NI, Cleton FJ, Osanto S (1997) Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev 23:209–240. https://doi.org/10.1016/s0305-7372(97)90012-8CrossRefPubMed

Crohns M, Liippo K, Erhola M et al (2009) Concurrent decline of several antioxidants and markers of oxidative stress during combination chemotherapy for small cell lung cancer. Clin Biochem 42:1236–1245. https://doi.org/10.1016/j.clinbiochem.2009.05.003CrossRefPubMed

Simone CB, Simone NL, Simone V (2007) Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival. Altern Ther Health Med 13:22–28PubMed

Facorro G, SarrasagueMM TH, Hager A et al (2004) Oxidative study of patients with total body irradiation: effects of amifostine treatment. Bone Marrow Transplant 33:793–798. https://doi.org/10.1038/sj.bmt.1704427CrossRefPubMed

Chen Y, JungsuwadeP VM, Butterfield DA, St Clair DK (2007) Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol Interv 7:147–156. https://doi.org/10.1124/mi.7.3.6CrossRefPubMed

SariI CA, Kaynar L, Saraymen R et al (2008) Disturbance of pro-oxidative/antioxidative balance in allogeneic peripheral blood stem cell transplantation. Ann Clin Lab Sci 38:120–125

Brea-Calvo G, Rodríguez-Hernández A, Fernández-Ayala et al (2006) Chemotherapy induces an increase in coenzyme Q10 levels in cancer cell lines. Free Radic Biol Med 40:1293–1302. https://doi.org/10.1016/j.freeradbiomed.2005.11.014CrossRefPubMed

10.

Sangeetha P, Das UN, Koratkar R, Suryaprabha P (1990) Increase in free radical generation and lipid peroxidation following chemotherapy in patients with cancer. Free Radic Biol Med 8:15–19. https://doi.org/10.1016/0891-5849(90)90139-aCrossRefPubMed

11.

White AC, Sousa AM, Blumberg J et al (2006) Plasma antioxidants in subjects before hematopoietic stem cell transplantation. Bone Marrow Transplant 38:513–520. https://doi.org/10.1038/sj.bmt.1705475CrossRefPubMed

12.

Clemens MR, Waladkhani AR, Bublitz K et al (1997) Supplementation with antioxidants prior to bone marrow transplantation. Wien Klin Wochenschr 109:771–776PubMed

13.

Fridovich I (1983) Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol 23:239–257. https://doi.org/10.1146/annurev.pa.23.040183.001323CrossRefPubMed

14.

Sugiyama S, Hayakawa M, Kato T et al (1989) Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity. Biochem Biophys Res Commun 159:1121–1127. https://doi.org/10.1016/0006-291x(89)92225-0CrossRefPubMed

15.

Zhang JG, Zhong LF, Zhang M, Xia YX (1992) Protection effects of procaine on oxidative stress and toxicities of renal cortical slices from rats caused by cisplatin in vitro. Arch Toxicol 66:354–358. https://doi.org/10.1007/bf01973631CrossRefPubMed

16.

Gill RA, Onstad GR, Cardamone JM et al (1982) Hepatic veno-occlusive disease caused by 6-thioguanine. Ann Intern Med 96:58–60. https://doi.org/10.7326/0003-4819-96-1-58CrossRefPubMed

17.

Stoneham S, Lennard L, Coen P et al (2003) Veno-occlusive disease in patients receiving thiopurines during maintenance therapy for childhood acute lymphoblastic leukemia. Br J Haematol 123:100–102. https://doi.org/10.1046/j.1365-2141.2003.04578.xCrossRefPubMed

18.

Lee WM (1995) Drug-induced hepatotoxicity. N Engl J Med 333:1118–1127. https://doi.org/10.1056/NEJM199510263331706CrossRefPubMed

19.

DeLeve LD, Shulman HM, McDonald GB (2002) Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis 22:27–42. https://doi.org/10.1055/s-2002-23204CrossRefPubMed

20.

Chughlay MF, Kramer N, Spearman CV et al (2016) N-acetylcysteine for non-paracetamol drug induced liver injury: a systematic review. Br J Clin Pharmacol 81:1021–1029. https://doi.org/10.1111/bcp.12880CrossRefPubMedPubMedCentral

21.

Koren G, Beatty K, Seto A et al (1992) The effects of impaired liver function on the elimination of antineoplastic agents. Ann Pharmacother 26:363–371. https://doi.org/10.1177/106002809202600311CrossRefPubMed

22.

Desai ZR, Van den Berg HW, Bridges JM, Shanks RG (1982) Can severe vincristine neurotoxicity be prevented? Cancer Chemother Pharmacol 8:211–214. https://doi.org/10.1007/bf00255486CrossRefPubMed

23.

Hohneker JA (1994) A summary of vinorelbine (Navelbine) safety datafrom north American clinical trials. Semin Oncol 21:42–46PubMed

24.

Van den Berg HW, Desai ZR, Wilson R et al (1982) The pharmacokinetics of vincristine in man: reduced drug clearance associated with raised serum alkaline phosphatase and dose-limited elimination. Cancer Chemother Pharmacol 8:215–219. https://doi.org/10.1007/bf00255487CrossRefPubMed

25.

Stewart CF, Arbuck SG, Fleming RA, Evans WE (1990) Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. J Clin Oncol 8:1874–1879. https://doi.org/10.1200/JCO.1990.8.11.1874CrossRefPubMed

26.

Raymond E, Boige V, Faivre S et al (2002) Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction. J Clin Oncol 20:4303–4312. https://doi.org/10.1200/JCO.2002.03.123CrossRefPubMed

27.

Neuman MG, Cameron RG, Haber JA et al (1999) Inducers of cytochrome P450 2E1 enhance methotrexate-induced hepatocytoxicity. Clin Biochem 32:519–536. https://doi.org/10.1016/s0009-9120(99)00052-1CrossRefPubMed

28.

Jahovic N, Cevik H, Sehirli AO et al (2003) Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats. J Pineal Res 34:282–287CrossRef

29.

Cetiner M, Sener G, Sehirli AO et al (2005) Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death. Toxicol Appl Pharmacol 209:39–50. https://doi.org/10.1016/j.taap.2005.03.009CrossRefPubMed

30.

Ali N, Rashid S, Nafees S et al (2017) Protective effect of chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: an experimental approach. Chem Biol Interact 272:80–91. https://doi.org/10.1016/j.cbi.2017.05.002CrossRefPubMed

31.

Szabo S (1984) Role of sulfhydryls and early vascular lesions in gastric mucosal injury. Acta Physiol Hung 64:203–214PubMed

32.

Ross D (1988) Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 37:231–249. https://doi.org/10.1016/0163-7258(88)90027-7CrossRefPubMed

33.

Babiak RM, Campello AP, Carnieri EG (1998) Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct 16:283–293. https://doi.org/10.1002/(SICI)1099-0844(1998120)16:4<283::AID-CBF801>3.0.CO;2-ECrossRefPubMed

34.

Manov I, Hırsh M, Iancu TC (2002) Acetaminophen hepatotoxicity and mechanisms of its protection by N-acetylcysteine: a study of Hep3B cells. Exp Toxicol Pathol 53:489–500. https://doi.org/10.1078/0940-2993-00215CrossRefPubMed

35.

Kumar O, Sugendran K, Vijayaraghavan R (2003) Oxidative stress associated hepatic and renal toxicity induced by ricin in mice. Toxicon 1:333–338. https://doi.org/10.1016/s0041-0101(02)00313-6CrossRef

36.

Akhgari M, Abdollahi M, Kebryaeezadeh A et al (2003) Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats. Hum Exp Toxicol 22:205–211. https://doi.org/10.1191/0960327103ht346oaCrossRefPubMed

37.

Tafazoli S, Spehar DD, O’Brien PJ (2005) Oxidative stress mediated idiosyncratic drug toxicity. Drug Metab Rev 37:311–325. https://doi.org/10.1081/dmr-55227CrossRefPubMed

38.

39.

Dervieux T, Brenner TL, Hon YY et al (2002) De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo. Blood 15:1240–1247. https://doi.org/10.1182/blood-2002-02-0495CrossRef

Titel: Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury
verfasst von: Nilgun Eroglu
Erol Erduran
Gokce Pinar Reis
Aysenur Bahadır
Publikationsdatum: 01.04.2020
Verlag: Springer London
Erschienen in: Irish Journal of Medical Science (1971 -) / Ausgabe 4/2020
Print ISSN: 0021-1265
Elektronische ISSN: 1863-4362
DOI: https://doi.org/10.1007/s11845-020-02219-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Background

Aims

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2020

Media coverage of major sporting events: alcohol, crowd shots and the Rugby World Cup 2019

A survey of general practitioner’s opinion on the proposal to introduce ‘treat and referral’ into the Irish emergency medical service

Bypass: an integrated hip fracture care pathway

Designing and assessing a urethral catheter skills workshop for intern doctors in a university teaching hospital

Follow-up study on transphyseal ACL reconstruction in Irish adolescents with no cases of leg length discrepancy or angular deformity